Inflammatory mediators, interaction with eosinophils and tyrosine kinase inhibitors effects on mast cells of sickle cell anemia patients

Abstract

The mast cells are derived from hematopoietic stem cells and migrate to their target tissues as immature cells. These cells are inflammatory resident in tissues known for the role in allergic hypersensitivity, but were recently implicated in many immune, vascular and sensorial function, including pain. In the last years, the participation of mast cells in chronic inflammatory diseases, like rheumatic arthritis and multiple sclerosis description have been increasing and suggests that mast cells can be an important target in the treatment for these diseases. The use of tyrosine kinase inhibitors (TKIs), through the inhibition of c-KIT receptor, present in mast cells, have been effective in the treatment of rheumatic arthritis, asthma, and multiple sclerosis. The authors suggest that when used in combination with other drugs available, the TKIs could improve the therapeutic management of these diseases. Recently, using transgenic animal model for sickle cell anemia (SCA), Vicent et al (2013) have shown that activation and degranulation of mast cells contribute to the pathophysiology of pain in the SCA, and the animals treatment with TKIs (Imatinib) improved hyperalgesia and prevented hypoxia/reoxygenation in these animals. However, the relationship of these cells in other SCA clinical symptoms is not clear. The mast cells and eosinophils are the main allergic inflammatory cells, and studies have demonstrated that the mast cells mediators can affect the eosinophils, and the opposite. Our group has been showing that eosinophils also have an important role in pathophysiology of SCA. Therefore, the goals of this project will be evaluate in vitro the mediators released by mast cells from patients with SCA, and analyze the influence of TKI treatment in mast cells activation and degranulation. In addition to, investigate if eosinophils/ mast cells interaction could change cellular activation. These analyses will be performed using the Amnis ImageStream apparatus, machine that we proposed acquire in this active thematic project. The flow citometry with image, ImageStream, join the flow citometry technique with optical microscopy and the fluorescence. Thus, is possible view the cellular morphology and immunofluorescence together with citometric results for each cells. Therefore this equipment is perfect to investigate the cellular activation.